E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway.
Acta Pharmacol Sin
; 33(6): 817-22, 2012 Jun.
Article
in En
| MEDLINE
| ID: mdl-22543706
ABSTRACT
AIM:
E-cadherin is unusually highly expressed in most ovarian cancers. This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers.METHODS:
Human ovarian adenocarcinoma cell line SKOV-3 was examined. E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi), and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment. E-cadherin-mediated Ca(2+)-dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells. The expression levels of E-cadherin, extracellular signal-related kinase (ERK), phosphorylated ERK (P-ERK) were measured using Western blot assays.RESULTS:
Transfection with CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells. E-cadherin-mediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK, but did not modify the expression of ERK protein. The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 (50 µmol/L), but not by the PI3K inhibitor wortmannin (1 µmol/L) or PKA inhibitor H89 (10 µmol/L).CONCLUSION:
E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.
Full text:
1
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Adenocarcinoma
/
Cadherins
/
MAP Kinase Signaling System
Limits:
Female
/
Humans
Language:
En
Year:
2012
Type:
Article